1. Field of the Invention
This invention relates to a new peptide antibiotic complex and to its production, recovery and separation into four bioactive antibiotic components.
2. Description of the Prior Art
The Bu-2470 antibiotic complex of the present invention comprises a mixture of co-produced individual antibiotic factors. Of the four major bioactive factors, one is a non-acylated octapeptide antibiotic and three are octapeptide antibiotics acylated with a fatty acid residue. The new antibiotics are produced by fermentation of a new strain of Bacillus designated Bacillus circulans strain G493-B6 (ATCC 31,805).
Several acylated octapeptide antibiotics have been described in the literature. Those produced by fermentation of Bacillus circulans strains include the following:
1. Antibiotic Bu-1880 disclosed in U.S. Patent 3,880,994 is an octapeptide acylated with a 3-hydroxy-8-methyldecanoic acid fatty acid residue. Bu-1880 is produced by fermentation of Bacillus circulans ATCC 21828 and contains the amino acids phenylalanine, leucine and .alpha.,.gamma.-diaminobutyric acid in a ratio of 1:2:5. While the structure of Bu-1880 has not yet been determined, Bu-1880 can be clearly differentiated from antibiotic components Bu-2470 A, B.sub.2a and B.sub.2b on the basis of its physicochemical properties and fatty acid moiety.
2. Japanese Published Patent Application 50/160,491 discloses the acylated octapeptide antibiotic 333-25 produced by fermentation of Bacillus circulans No. 333-25 (FERM-P2362) (see also J. Antibiotics 29:516-520, 1976). Antibiotic 333-25 is described in J. Antibiotics 29 (12):1339-1340 (1976) as having the structure ##STR1## wherein Dab is .alpha.,.gamma.-diaminobutyric acid, Phe is phenylalanine and Leu is leucine. The 333-25 antibiotic can be differentiated from the antibiotics of the present invention by the presence of the .beta.-hydroxy anteisononanoyl fatty acid moiety.
3. The antibiotic complex EM-49 is disclosed in U.S. Pat. No. 3,856,938 as being produced by fermentation of Bacillus circulans ATCC 21656. The complex consists of four major components, .alpha.,.beta.,.gamma. and .delta.. which are cyclic octapeptides monoacylated with .beta.-hydroxy fatty acids. The four components are distinguishable by their amino acid compositions and variations in the structure of their fatty acid moieties. EM-49 .alpha. and .beta. contain no phenylalanine, five residues of 2,4-diaminobutyric acid and three residues of leucine. EM-49 .gamma. and .delta. contain one residue of phenylalanine, two residues of leucine and five residues of 2,4-diaminobutyric acid. EM-49 .alpha. and .beta. differ from each other in the structures of the fatty acid moieties. EM-49 .gamma. and .delta. differ from each other in the same way. [see also J. Chromatography 97:112-114 (1974) and J. Antibiotics 26:444-448 (1973)]. From J. Antibiotics 28:379-389 (1975) and J. Antibiotics 29:1241-1242 (1976), the structures of the EM-49 antibiotics (including further subfactors of .alpha. and .gamma. may be represented as follows: ##STR2## The EM 49 antibiotics differ from the compounds of the present invention in their amino acid compositions.
The antibiotic Y-8495 produced by fermentation of Bacillus bungoensis (FERM-P 2143) is disclosed in Japanese Published Patent Application 50/25,795. Y-8495 is an octapeptide antibiotic, but it can be differentiated from the compounds of the present invention on the basis of its physicochemical properties.